MINI REVIEW published: 02 February 2017 doi: 10.3389/fnhum.2017.00044
Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex in Schizophrenia: A Quantitative Review of Cognitive Outcomes Joshua E. Mervis 1*, Riley J. Capizzi 1 , Elias Boroda 2 and Angus W. MacDonald III 1, 3 1
Department of Psychology, University of Minnesota, Minneapolis, MN, USA, 2 Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA, 3 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
Edited by: Evangelia G. Chrysikou, University of Kansas, USA Reviewed by: Josefien Dedoncker, University Hospital Ghent, Belgium Hector Arciniega, University of Nevada, Reno, USA *Correspondence: Joshua E. Mervis [email protected] Received: 09 September 2016 Accepted: 20 January 2017 Published: 02 February 2017 Citation: Mervis JE, Capizzi RJ, Boroda E and MacDonald AW III (2017) Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex in Schizophrenia: A Quantitative Review of Cognitive Outcomes. Front. Hum. Neurosci. 11:44. doi: 10.3389/fnhum.2017.00044
Cognitive deficits are a core and disabling feature of psychotic disorders, specifically schizophrenia. Current treatments for impaired cognition in schizophrenia remain insufficient. Recent research suggests transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex can potentiate cognitive improvements in healthy individuals and those with psychiatric conditions, such as schizophrenia. However, this burgeoning literature has not been quantitatively evaluated. Through a literature search and quantitative review, we identified 194 papers on tDCS, psychosis, and cognition. Selection criteria included pre/post design and sham control to achieve specific sham-adjusted effect sizes. The 6 retained studies all address schizophrenia populations and include single and repeated stimulation, as well as within and between subject designs. Small positive effects were found for anodal stimulation on behavioral measures of attention and working memory, with tentative findings for cognitive ability and memory. Cathodal stimulation yielded a small positive effect on behaviorally measured cognitive ability. Neurophysiological measures of attention showed a small to medium down-modulation effect for anodal stimulation. Implications of these findings and guidelines for future research are discussed. As revealed by this report, due to the paucity of data available, much remains unknown regarding the clinical efficacy of tDCS in schizophrenia. Keywords: cognition, dorsolateral prefrontal cortex, quantitative review, Schizophrenia, transcranial direct current stimulation
INTRODUCTION Impaired cognition is a significant and disabling feature of psychotic disorders such as schizophrenia. Deficits in executive functions (working memory, attention, response inhibition) are the most commonly reported, and the most predictive of functional outcome (Green, 1996). Despite the central role of these impairments, current treatments, including pharmacological interventions, have proven ineffective at ameliorating cognitive dysfunction (Fusar-Poli et al., 2015). New or adjunctive treatment options are needed.
Frontiers in Human Neuroscience | www.frontiersin.org
1
February 2017 | Volume 11 | Article 44
Mervis et al.
tDCS, Cognition, and Schizophrenia
OR “direct current”). Published articles were collected up until May 2016 returning 194 results.
A large body of evidence implicates impaired frontal cortical activity as a causal factor in cognitive dysfunction in schizophrenia (Minzenberg et al., 2009). Specifically, hypoactivation of the dorsolateral prefrontal cortex (DLPFC) has been suggested as the core deficit (Potkin et al., 2009; Lesh et al., 2011). Given the pivotal role of the DLPFC in mediating a wide range of executive functions (Niendam et al., 2012), interventions that target this region are of great clinical interest. Non-invasive methods of neuromodulation provide a safe, cost-effective and robust means to enhance DLPFC function. Transcranial current stimulation (tCS) is a non-invasive neuromodulation technique that uses small, specifically directed electrical currents to alter cortical brain activity (Nitsche and Paulus, 2001). Though there are several forms of tCS, transcranial direct current stimulation (tDCS) has by far been the most commonly employed. TDCS involves the use of two electrodes, a positively charged anode and a negatively charged cathode. Studies in both animals and humans demonstrate that anodal stimulation produces a shift in excitability that depolarizes neurons, while cathodal stimulation has opposite effects (Nitsche and Paulus, 2000; Cambiaghi et al., 2010). Though the mechanisms underlying tDCS are still under investigation, it is postulated that these shifts in excitability are induced by altering membrane polarization at the cellular level (Fritsch et al., 2010; Kronberg et al., 2017). Due to its safety (Bikson et al., 2016), tolerability, and low cost, the use of tDCS has grown substantially. Recent research demonstrates that tDCS targeted to the DLPFC has the ability to potentiate changes in cognition in both healthy individuals (Fregni et al., 2005) and those with various psychiatric conditions, such as schizophrenia (Dedoncker et al., 2016). As a clinical intervention, the use of tDCS to enhance cognition in schizophrenia is especially promising. Anodal tDCS, directed at the DLPFC, has now been evaluated in several trials as a possible rehabilitation technique or adjunct to existing treatments (Minzenberg and Carter, 2012; Palm et al., 2016). However, research has indicated contradictory effects of stimulation in some patient populations (Berryhill et al., 2014) and differential effects on various cognitive domains are not well understood. To address these ambiguities, we undertook a quantitative review of studies on tDCS in schizophrenia using the PubMed database and identified 194 articles. This number was reduced to 6 articles after excluding studies on populations without psychosis, without cognitive outcomes, and including only those with a sham stimulation condition to create a sham-adjusted effect size. Study outcomes and heterogeneity of designs were aggregated and variance-weighted.
Eligibility Criteria Criteria for inclusion were: (a) psychosis; (b) randomized and sham-controlled designs; (c) pre-post within-subject or betweensubject designs. Duplicates, reviews, case studies, and studies with
Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex in Schizophrenia: A Quantitative Review of Cognitive Outcomes Joshua E. Mervis 1*, Riley J. Capizzi 1 , Elias Boroda 2 and Angus W. MacDonald III 1, 3 1
Department of Psychology, University of Minnesota, Minneapolis, MN, USA, 2 Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA, 3 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
Edited by: Evangelia G. Chrysikou, University of Kansas, USA Reviewed by: Josefien Dedoncker, University Hospital Ghent, Belgium Hector Arciniega, University of Nevada, Reno, USA *Correspondence: Joshua E. Mervis [email protected] Received: 09 September 2016 Accepted: 20 January 2017 Published: 02 February 2017 Citation: Mervis JE, Capizzi RJ, Boroda E and MacDonald AW III (2017) Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex in Schizophrenia: A Quantitative Review of Cognitive Outcomes. Front. Hum. Neurosci. 11:44. doi: 10.3389/fnhum.2017.00044
Cognitive deficits are a core and disabling feature of psychotic disorders, specifically schizophrenia. Current treatments for impaired cognition in schizophrenia remain insufficient. Recent research suggests transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex can potentiate cognitive improvements in healthy individuals and those with psychiatric conditions, such as schizophrenia. However, this burgeoning literature has not been quantitatively evaluated. Through a literature search and quantitative review, we identified 194 papers on tDCS, psychosis, and cognition. Selection criteria included pre/post design and sham control to achieve specific sham-adjusted effect sizes. The 6 retained studies all address schizophrenia populations and include single and repeated stimulation, as well as within and between subject designs. Small positive effects were found for anodal stimulation on behavioral measures of attention and working memory, with tentative findings for cognitive ability and memory. Cathodal stimulation yielded a small positive effect on behaviorally measured cognitive ability. Neurophysiological measures of attention showed a small to medium down-modulation effect for anodal stimulation. Implications of these findings and guidelines for future research are discussed. As revealed by this report, due to the paucity of data available, much remains unknown regarding the clinical efficacy of tDCS in schizophrenia. Keywords: cognition, dorsolateral prefrontal cortex, quantitative review, Schizophrenia, transcranial direct current stimulation
INTRODUCTION Impaired cognition is a significant and disabling feature of psychotic disorders such as schizophrenia. Deficits in executive functions (working memory, attention, response inhibition) are the most commonly reported, and the most predictive of functional outcome (Green, 1996). Despite the central role of these impairments, current treatments, including pharmacological interventions, have proven ineffective at ameliorating cognitive dysfunction (Fusar-Poli et al., 2015). New or adjunctive treatment options are needed.
Frontiers in Human Neuroscience | www.frontiersin.org
1
February 2017 | Volume 11 | Article 44
Mervis et al.
tDCS, Cognition, and Schizophrenia
OR “direct current”). Published articles were collected up until May 2016 returning 194 results.
A large body of evidence implicates impaired frontal cortical activity as a causal factor in cognitive dysfunction in schizophrenia (Minzenberg et al., 2009). Specifically, hypoactivation of the dorsolateral prefrontal cortex (DLPFC) has been suggested as the core deficit (Potkin et al., 2009; Lesh et al., 2011). Given the pivotal role of the DLPFC in mediating a wide range of executive functions (Niendam et al., 2012), interventions that target this region are of great clinical interest. Non-invasive methods of neuromodulation provide a safe, cost-effective and robust means to enhance DLPFC function. Transcranial current stimulation (tCS) is a non-invasive neuromodulation technique that uses small, specifically directed electrical currents to alter cortical brain activity (Nitsche and Paulus, 2001). Though there are several forms of tCS, transcranial direct current stimulation (tDCS) has by far been the most commonly employed. TDCS involves the use of two electrodes, a positively charged anode and a negatively charged cathode. Studies in both animals and humans demonstrate that anodal stimulation produces a shift in excitability that depolarizes neurons, while cathodal stimulation has opposite effects (Nitsche and Paulus, 2000; Cambiaghi et al., 2010). Though the mechanisms underlying tDCS are still under investigation, it is postulated that these shifts in excitability are induced by altering membrane polarization at the cellular level (Fritsch et al., 2010; Kronberg et al., 2017). Due to its safety (Bikson et al., 2016), tolerability, and low cost, the use of tDCS has grown substantially. Recent research demonstrates that tDCS targeted to the DLPFC has the ability to potentiate changes in cognition in both healthy individuals (Fregni et al., 2005) and those with various psychiatric conditions, such as schizophrenia (Dedoncker et al., 2016). As a clinical intervention, the use of tDCS to enhance cognition in schizophrenia is especially promising. Anodal tDCS, directed at the DLPFC, has now been evaluated in several trials as a possible rehabilitation technique or adjunct to existing treatments (Minzenberg and Carter, 2012; Palm et al., 2016). However, research has indicated contradictory effects of stimulation in some patient populations (Berryhill et al., 2014) and differential effects on various cognitive domains are not well understood. To address these ambiguities, we undertook a quantitative review of studies on tDCS in schizophrenia using the PubMed database and identified 194 articles. This number was reduced to 6 articles after excluding studies on populations without psychosis, without cognitive outcomes, and including only those with a sham stimulation condition to create a sham-adjusted effect size. Study outcomes and heterogeneity of designs were aggregated and variance-weighted.
Eligibility Criteria Criteria for inclusion were: (a) psychosis; (b) randomized and sham-controlled designs; (c) pre-post within-subject or betweensubject designs. Duplicates, reviews, case studies, and studies with
